Bronchoalveolar lavage and plasma Antithrombin and cytokines in inhalation and burn injury: a pilot study.

Systemic inflammatory response syndrome (SIRS) is initiated during the acute phase of thermal injury. The objective was to determine the SIRS impact on cytokine and Antithrombin (AT) levels in smoke inhalation and burn injury. This observational pilot study compared plasma and bronchoalveolar lavage fluid (BAL) cytokine and AT levels in the first six days post smoke inhalation and burn injury. Twenty-five patients, 14 with inhalation + burn injury > 10% total body surface area (TBSA) and 11 with inhalation injury and ≤ 10% TBSA participated. Human Th1/Th2 cytometric bead array kit from BD Biosciences Pharmingen determined cytokine levels; AT levels with Sigma Diagnostics and spectrophotometry. Results indicated no significant age difference between the two groups (42.1 ± 7.2) versus 49.6 ± 6.4 years. On admission, the inhalation group had 5.4 ± 3.9% TBSA compared to 35.0 ± 22.2% TBSA in the inhalation + burn group, P < 0.001. Comparing groups, AT plasma levels were significantly decreased (P = 0.025) and IL-2 levels significantly increased (P = 0.025) in the inhalation + burn group compared to the inhalation group; there was no significant difference in BAL AT or cytokine levels. Combined group plasma AT levels (65.41 ± 4.44%) were significantly increased compared to BAL AT levels (1.06 ± 0.71%), P < 0.001. In contrast, BAL TNF-α levels (35.61 ± 16.01 pg/ml) were significantly increased in relation to the plasma levels (4.68 ± 1.27 pg/ml), P = 0.02. On days 1-2, AT plasma levels were significantly decreased in the inhalation + burn group (41.01 ± 5.24%) compared to the inhalation group (81.02 ± 10.99%), P = 0.002. IL-6 plasma levels were higher in the inhalation + burn group compared to the inhalation group on admission, but both levels decreased by days 3-6. IL-6 BAL levels were elevated in both groups on days 1-2 and decreased by days 3-6. In the first six days of resuscitation, all plasma cytokines were increased in the two groups compared to controls. AT plasma and BAL levels were significantly reduced in both groups, contributing to the coagulopathy. Increased BAL TNF-α and IL-6 levels may have contributed to the pulmonary perturbations during the initial SIRS response in both groups.

Heparin resistance in acute coronary syndromes.

BACKGROUND: Maintaining a therapeutic level of anticoagulation with unfractionated heparin remains a major challenge for clinicians because of the wide variability of patient responses, which may be explained by variable binding of heparin to plasma proteins. Direct thrombin inhibitors may offer an advantage in more predictable anticoagulation. METHODS: Plasma samples from normal volunteers, stable coronary artery disease (CAD) patients, unstable angina patients, and acute myocardial infarction patients were obtained. A fixed concentration of heparin (.13 U/ml) or bivalirudin (1.6 microg/ml) was added to plasma from each of the four study groups and measurement of the APTT was performed. In addition, a pool of plasma from patients with acute MI was diluted in pooled normal plasma, and heparin or bivalirudin was added to the plasma preparation and APTT measurements performed. RESULTS: In heparin-treated plasma samples, mean APTT values were 443 +/- 137% baseline for normal volunteers, 347 +/- 116% for patients with stable CAD, 290 +/- 124% for patients with unstable angina (p < 0.05), and 230 +/- 120% for patients with acute MI (p < 0.05). APTT did not differ across the four groups treated with bivalirudin. There was a much higher degree of variability in APTT values in heparin treated controls (272%-671%, SD approximately 30%) compared to bivalirudin treated controls (284-499%, SD approximately 12%). When the "acute MI pool" was diluted in pooled normal plasma at fixed concentrations of either bivalirudin (1.6 mug/ml) or heparin (0.13 U/ml), there was a sharp decrease in heparin activity from 407% baseline (at 0% acute MI pool) to values as low as 126% baseline (at 100% acute MI pool). A markedly different pattern was seen in the bivalirudin treated samples, where a trend towards decreased APTT values was seen only at the 100% acute MI pool. CONCLUSION: Both heparin variability and resistance may limit optimal antithrombotic therapy with heparin in patients with ACS and constitutes a potential advantage of direct antithrombin blockade with bivalirudin.

Elevated cytokine levels in peritoneal fluid from burned patients with intra-abdominal hypertension and abdominal compartment syndrome.

BACKGROUND: Burn patients with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) undergo vigorous resuscitation and accumulate peritoneal fluid (PF) that is a plasma ultra-filtrate. This study compared antithrombin (AT) and cytokine levels in burn patient plasma and peritoneal fluid (PF). METHODS: Twenty-nine patients were studied: 22 developed IAH and 9 progressed to ACS. Burn + inhalation injury was present in 22 patients; 5 had burn only and 2 had inhalation only. Sixteen patients died: of these, 9 survived less than 48 h due to the severity of their injuries. Flow cytometry utilized the Cytometric Bead Array kit for Human Th1/Th2 cytokines. AT levels were determined by the Accucolor method spectrophotometrically. RESULTS: All cytokine levels were significantly elevated in burn plasma and PF compared to normal plasma, p < 0.001. AT plasma levels were decreased compared to normal. AT and cytokines were present in peritoneal fluid of burn patients with IAH and ACS. Patients who died had decreased plasma levels of AT and increased IFN-gamma, IL-10, IL-6, IL-4, IL-2 peritoneal fluid levels compared to survivors. CONCLUSIONS: Peritoneal fluid may be a reservoir for cytokines during initial resuscitation and contributes to homeostatic perturbations in burn patients.